Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• dendrimer. Therefore, we settled on first coupling Nα-Fmoc-Nε-(4-methyltrityl)-L-lysine (17) to the dendrimeric amine 18 by standard HATU amide coupling conditions (Scheme 3). The protecting groups were chosen specifically for selective deprotection and compatibility with the TAMRA fluorophore, which is

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• , the yield was lower (Scheme 2). In order to bring about the cleavage of the benzyl protecting groups in the ketones 8a and 8b by hydrogenolysis [17][18], various metal catalysts were tested. It turned out that palladium on charcoal was the only catalytic system that provided satisfying results. Ethyl

• , 69.56; H, 6.73. General procedure for the synthesis of phenols 9–11 by hydrogenolytic cleavage of benzyl ether protecting groups: An autoclave was equipped with a stirring bar and charged with O-protected dihydrostilbenes 8a,b (0.8 mmol), palladium on charcoal (50 mg) and ethyl acetate (12 mL). The

• -catalyzed addition of ketones 6 to styrenes 7. Yields: 8a: 65%; 8b: 68%; 8c: 73%; 8d: 40%. Cleavage of benzyl protecting groups in ketones 8a and 8b. Synthesis of scorzodihydrostilbene aglycon 9. Synthesis of glycoside 12 and deprotected epi-scorzodihydrostilbene D (13). Yields of isolated products: 12: 14

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• components can significantly diversify the synthetic output of MMCRs. However, a limiting factor in the design of MMCRs with such components is the risk of generating undesired cross-adducts. This problem can be avoided by introduction of protecting groups or through the sequential generation of repeating

• course of a given MCR can trigger a new one, then allowing for selectivity in another sequential approach. Finally, the use of protecting groups in reactants undergoing MCRs leads to multistep transformations which, after suitable deprotections, selectively afford the final adducts. Active research is

• pursued in the field, aiming at the generalization of the aforementioned concepts and their extension to diverse synthetic outcomes. Selectivity levels found in multiple multicomponent reactions. I) Innate selectivity; II) sequential selectivity; III) use of biased substrates; IV) use of protecting groups

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• in the β-anomer form ( −58.7°) in 62% yield, while the benzoylated analogue 4b ( −44.0°) was obtained in lower yields of 40% (Scheme 1). Acetyl and benzoyl protecting groups were then removed from 4a and 4b in anhydrous methanol saturated with dry ammonia at 0 °C, to afford NR+Cl− ( −28.6°) in good

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• ). Dihydroxylation of the C=C bond gave a 10:1 mixture with (2S,3S,4R)-121 as a major product which was transformed into the isopropylidene derivative (2S,3S,4R)-122 to facilitate purification. Hydrogenolysis allowed to remove the N- and O-protecting groups and was followed by the spontaneous cyclization to a

• compound underwent another intramolecular cyclization in the 5-exo mode to form the oxazolidinone 118. To complete the synthesis of (2S,3S,4S)-4 the secondary hydroxy group was protected as a pivalate, the hydroxymethyl fragment was oxidized after hydrolysis of the silyl ether and finally all protecting

• groups were removed by concentrated acid. A very efficient synthesis of (2S,3S,4S)-4 starts from another serine-derived chiron, namely O-benzyl-N-Boc-D-serine [111], which was readily transformed to the Z-olefin 120 containing a benzophenone imine residue as a nitrogen protecting group (Scheme 29

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• group was the key for the high efficiency of this coupling. Similarly, condensation between peracylated GlcA donor 3 and 4 gave disaccharide 5 in excellent 97% yield (Scheme 2). The cyclic silylene group was then replaced by two acetyl groups because it is well-known that cyclic protecting groups at

• % of TMSOTf with respect to the donor, 0 ºC, CH2Cl2 as solvent). As mentioned before, it has been reported that cyclic protecting groups like 4,6-O-benzylidene acetals in GalNAc trichloroacetimidates lead to the formation of α/β mixtures in glycosylations involving GlcA acceptors [43][47]. However

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• -protecting groups, such as a benzyl group, at either the donor, the acceptor or at both. With the 6-O-Bn donor 16 a slightly diminished, but still respectable, 49% yield of the desired product 19 was obtained (Scheme 3). However, when using the 6-O-TBDPS donor 15 (1.2 equiv) a 60% isolated yield of the

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• in high chemical yield and purity by strategically introducing differentially protected dibasic amino acids such as lysine whose α- and ε-amino groups are protected as base labile Fmoc and trifluoroacetyl (Tfa) protecting groups, respectively. The whole concept is successfully illustrated using

• commonly available and less expensive cysteine-labelled 2-chlorotrityl resin (Figure 1b). The methodology is general and can be significantly useful for acid-sensitive resins that contain acid-labile orthogonal amino acids with 4-methoxytrityl (Mmt) and 4-methyltrityl (Mtt) protecting groups. Results and

• (Pg) to give tetrapeptides 8a or 8b. The tetrapeptides 8a or 8b were tethered sequentially to 8-aminocaprylic acid, two phenyalanine residues, another 8-aminocaprylic acid and finally to DUPA precursor 4, to provide polypeptide chains 9a or 9b (Scheme 2). The ε-amino protecting groups present in the

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• functionalised phenothiazine demonstrated an equipotent MIC value in direct comparison to the parent phenothiazine from which it was derived. The final conjugate was synthesised by amide bond formation between the two components and global deprotection of the PMB protecting groups to unmask the catechol iron

• azotochelin. Catechol-based siderophores can act as xenosiderophores and be recognised for uptake by Gram-negative bacteria and mycobacteria [14][15]. Most commonly benzyl protecting groups are used in the synthesis of catechol siderophores and cleaved in the final step by palladium catalysed hydrogenation

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• , avoiding the use of protecting groups, and affording the desired heterocycles in good to excellent overall yields. A suitable balance between reactivity and selectivity was achieved in the SNAr reaction which, to our knowledge, is the first report on a successful uncatalyzed N-monoarylation of the

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• hand, we finally accomplished the N-acylation reaction using n-BuLi in THF at −60 °C [15] in 60% yield. Removal of both protecting groups by catalytic hydrogenation, gave the desired compound 1 in 72% yield (Scheme 3). Compound 1 was subjected to a preliminary study to evaluate the antimicrobial

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• Organische Chemie, Universität Münster, Corrensstrasse 40, 48149 Münster, Germany 10.3762/bjoc.14.217 Abstract Copper(I)-promoted "click" cyclization in the presence of TBTA afforded nucleoside macrocycles in very high yields (≈70%) without using protecting groups. To this end, dU and dC derivatives

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• with different protecting groups, resulting in cumbersome steps and high costs. To reduce the synthetic steps and simplify the operations, we developed a new semi-synthesis of spinetoram J based on a self-protection strategy (Scheme 2). In this study, 3-O-ethyl-2,4-di-O-methylrhamnose was used not only

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• was converted to 6a as previously described in [23]. Next, the isopropylidene group at positions 4 and 5 were removed under acidic conditions and the resulting intermediate 7a was converted to 7b with identical protecting groups at positions 3, 4 and 5 [24][25][26][27][28]. In order to obtain D

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• protected naturally occurring amines such as GABA and phenylethylamine as well as diamines with orthogonal protecting groups, cf. product 2c. The combination of this protocol with the diastereoselective reductive amination reported by Hughes and Devine [41], provides access to very high value chiral α

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• . Deprotection was performed by oxidation followed by treating with a weak base. The yields were good to excellent. The new amino protecting group offers a different dimension of orthogonality in reference to the commonly used amino protecting groups in terms of deprotection conditions. It is expected to allow a

• collection of transformations to be carried out on the protected substrates that are unattainable using any known protecting groups. Keywords: amine; carbamate; dM-Dmoc; oxidation; protecting group; Introduction In multistep organic synthesis, amino groups usually have to be protected [1]. Protecting

• groups for the purpose mainly include those deprotectable by acid (e.g., tert-butyloxycarbonyl (Boc) group) [2][3][4], base (e.g., 9-fluorenylmethyloxycarbonyl (Fmoc) group and trifluoroacetyl group) [5][6][7], catalytic hydrogenation (e.g., benzyl group) [8], photoirradiation (e.g., 2-nitrophenylethyl

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• reaction with phenol to stereoselectively achieve the respective β-mannoside 82 in good yield (Scheme 14) [60]. This stereo-differentiating effect of isopropylidene protecting groups was also observed in other cases with D-mannopyranose [46][61]. It might be used as a key to a reliable approach to

• otherwise difficult to synthesize β-mannosides using the Mitsunobu procedure. This approach to 1,2-cis-mannosides is equally effective when cyclohexylidene protecting groups are used [28][47][62]. Mitsunobu glycosylation was also a successful method in total synthesis. In the course of a 17-step synthesis

• of hygromycin A, Donohoe et al. used a Mitsunobu glycosylation of 84 with the arabinose derivative 83. This reaction could be tuned to deliver the required β-arabinofuranoside building block 85 with high stereoselectivity and under the assistance of triisopropylsilyl (TIPS) protecting groups (Scheme

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• reaction of trans-cyclobutane sulfoxide 59. The authors concluded that the stereochemistry of the sulfoxide and the nature of the protecting groups had no significant effect on the yield of the Pummerer-type glycosylation [47] (Scheme 8). Pummerer-type glycosylation, which was developed by our group

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• yields (51–91%) and uniformly high enantioselectivities (92–99% ee), as shown in Scheme 1. Common protecting groups (R1), such as methyl, ethyl, 4-methoxybenzyl, methoxymethyl, phenyl and benzyl, were tolerated as well as various substituents (R2) on the aromatic ring of the isatins, including electron

• )substituted isatin imines (R1 = Me, Bn, H). Moreover, a range of electron-withdrawing and electron-donating groups on the aryl moiety (R2) as well as different N-carbamoyl protecting groups (R3 = t-Bu, Et, Bn) were compatible, providing generally high enantioselectivities (85 to >99% ee), except for the 5

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• derivative [17][18]. The C(sp2)–N cross-coupling of the triflate was achieved with benzophenone imine or benzylamine. The removal of the protecting groups resulted in 3-aminoestrone in high yields. Schön et al. developed two convenient protocols for the preparation of 3-aminoestrone using Pd(OAc)2 and Pd2

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• the use of orthogonal protecting groups (Figure 1A). Previous studies indicated that the free ε-amino group of Lys does not have an impact on the biological activity [15][17]. To prove our assumption, a set of novel cyclic NGR peptide–Dau conjugates were developed in which the Lys was replaced by

• was observed in the case of conjugates 2, 3 and 4 obtained with a lower yield. The improvement was observed especially in the cyclization step that might be explained by the lack of bulky protecting groups on amino acids used instead of Lys. Chemostability of cyclic NGR peptide–daunomycin conjugates

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• improvement can be explained by a protonation of TMSN3 causing the in situ generation of highly reactive HN3 (Scheme 3). Additionally, no acidic work-up, as described by Miyashita et al., was necessary to gain the free alcohol on C5, which corroborates the proposed mechanism. The protecting groups were

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• proved to be the most promising compound. The fluorine on 29 was replaced with a methoxy group after re-installing the isopropylidene protecting group. The cyano group was then converted to an amide and the methoxy converted to a hydroxy group. Removal of the protecting groups on the sugar gave 25, which

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• homogenate. Results and Discussion Synthesis of oxime bond-linked GnRH-III–[4Ser/Lys(Bu), 6Aaa, 8Lys(Dau=Aoa)] bioconjugates The GnRH-III bioconjugates were prepared as shown in Scheme 1. All peptides were synthesized by standard Fmoc-SPPS using orthogonal lysine protecting groups. Fmoc-Lys(Dde)-OH was

• aminooxyacetic acid as “carbonyl capture” reagent (2 h, at room temperature (rt)) resulted in the simultaneous removal of the side chain protecting groups and the cleavage of the peptide from the resin [54]. Peptides were isolated by precipitation with ice-cold Et2O, centrifuged, washed 3 times, dissolved in

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• practical reasons, the method was elaborated for the methylated derivatives of hextitol pendants it might be, eventually, applied also for synthons with other protecting groups. Experimental General The NMR spectra were recorded with a Varian VNMRS 600 MHz spectrometer for solutions in CDCl3 at 25 °C. The